Childhood leukemia (CL) rates among children with Hispanic ethnicity are among the highest in the world, although little is known about the mechanisms and determinants underlying this observation. CL risk is widely thought to be modulated by the interplay between individual genetic susceptibility and exposure to environmental and endogenous substances. The long-term goal of the proposed research is to identify combinations of specific genetic factors and environmental exposures that cause children with Hispanic ethnicity to have elevated rates of CL. With its diverse Hispanic population comprised primarily of pure indigenous and mixed (mestizo) indigenous-European peoples, as well as the widespread use of biomass fuels for heating and cooking, Guatemala presents an ideal model system to study exposure to suspected carcinogenic combustion products in an ethnic population most at risk for this disease. Before such a study could be undertaken in Guatemala, however, a pilot study is required to establish the feasibility of conducting an epidemiologic assessment in this largely understudied population. Such a pilot would also provide the opportunity to identify unforeseen barriers and subsequently modify the protocols to overcome such barriers. Therefore, the aims of the proposed pilot study include identifying and enrolling 50 children with incident CL from a tertiary pediatric oncology hospital in Guatemala City and 50 age, sex, and urban vs. rural status matched healthy controls (identified as healthy siblings of cardiovascular pediatric patients at an adjacent tertiary cardiovascular referral center). Additional aims include the development, validation, and administration of a valid survey instrument to record exposure to relevant epidemiologic and environmental exposures for CL, and to collect diagnostic bone marrow and remission peripheral blood on cases, and saliva on cases, controls, and their parents. Success for this pilot study will be measured by response rates for subject recruitment and biospecimen collection, results of a survey instrument validity sub-study, and comparability of cases and controls. If successful, this proposed study will motivate a full case-control study of the genetic and environmental epidemiology of childhood leukemia in Guatemala. Such a study would fill in gaps in what is known about the tumor biology of CL, of inherited genetic susceptibility associated with Hispanic ethnicity, and of putative causal relationships with products of combustion and risk. PUBLIC HEALTH RELEVANCE: A case-control study of childhood leukemia in Guatemala can fill important gaps in our knowledge about its epidemiology, including the observed elevation in rates among children of Hispanic ethnicity and the putative causal relationship of exposure to environmental products of combustion. To establish the feasibility of conducting a full epidemiologic study of the genetic and environmental epidemiology in Guatemala, a largely understudied population, we propose to conduct an initial pilot study. In this pilot, we plan to enroll 50 cases of childhood leukemia and 50 matched healthy controls, to obtain detailed information on relevant environmental and epidemiologic exposures, and to collect biospecimens for future molecular and genetic studies. The success of the pilot project will provide preliminary data to motivate a future full case-control study.